Cardiovascular disease is still the number one cause of death in the United States and risk factor reduction in primary care settings remains a critical challenge. Recently, we showed that a personalized health planning approach that incorporates mind-body techniques, such as mindfulness, significantly reduced the Framingham Risk score in primary care patients who exhibited one or more traditional cardiovascular risk factors. It is now critical that this intervention be extended to target reduction in psychological, metabolic and inflammatory factors that in prospective studies have been shown to predict new cases of coronary heart disease (CHD). The proposed Phase III randomized controlled trial will evaluate the efficacy of a 6-month Mindfulness-Based Personalized Health Plan (MB-PHP) in reducing (a) the combination of psychological risk factor (PRF) of severity of depressive symptoms, hostility and anger shown to predict 20-year incidence of CHD and (b) insulin resistance (IR). We will also examine whether reductions in psychological risk factors and insulin resistance contribute to a reduction in inflammation in the circulation and at the cellular/molecular level via attenuation of stress-induced cardiovascular and adrenergic responses and arousal of negative affect, both shown to predict inflammatory cellular markers. The MB-PHP will use mindfulness training to promote reduction in psychological risk factors and stress-induced arousal of negative affect while supporting PHP-targeted improvements in diet and exercise that will contribute to reduction in insulin resistance. The Anger Recall Interview (ARI) will be used prior to and at the completion of the intervention to assess stress-induced changes in cardiovascular and adrenergic responses as well as arousal of negative affect. Initial clinic screening of 2200 will identify 550 primary care patients who meet entry criteria for elevated psychological risk factor score (> .6). Of the 550 patients we will identify 220 who also exhibiting insulin resistance (> 1.96) as calculated by the Homeostasis Assessment model. Subjects will be randomized to either MB-PHP or attention support control. We hypothesize that, relative to the attention support group, the subjects in the MB-PHP will show (a) greater decreases in PRF and IR; (b) greater reduction in stress-induced arousal of negative affect to the ARI; (c) greater pre- to post-treatment decreases in cardiovascular and adrenergic responses to the ARI and (d) Treatment-related reductions in arousal of negative affect and cardiovascular and adrenergic responses to the ARI, alone and in combination with treatment-related changes in PRF and IR, will predict pre- to post-treatment decreases in circulating levels of plasma interleukin (IL)-6 and C-reactive protein (CRP), as well as attenuated stress-induced changes in in vitro cellular adhesion molecules (CD11/CD18) expression, stimulated production of proinflammatory cytokines by peripheral blood mononuclear cells and changes in vivo IL-6 and CRP. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is still the number one cause of death in the United States and risk factor reduction in primary care settings remains a critical challenge. The clinical relevance of the proposed intervention is in concomitantly targeting of psychological factors and insulin resistance that are likely to reduce inflammation and thus decrease the risk of future cardiovascular disease in asymptomatic, yet at risk, primary care patients.